Clinical case seminar

Rapid pituitary tumor shrinkage with dissociation between antiproliferative and antisecretory effects of a long-acting octreotide in an acromegalic patient

Eugenia Resmini, Patrizia Dadati, Jean Luis Ravetti, Gianluigi Zona, Renato Spaziante, Alexandru Saveanu, Philippe Jaquet, Michael D. Culler, Federico Bianchi, Alberto Rebora, Francesco Minuto, Diego Ferone

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Context: Criteria to define the response to somatostatin (SS) analogs (SSA) in acromegaly are based on biochemical control of the disease. However, the mechanisms of action of SSAs in inhibiting tumor growth and hormonal secretion are only partially understood, and the two effects may occur independently. Objective: The objective of the study was to investigate the dissociation between antiproliferative and antisecretive effects of SSA in an octreotide-resistant patient displaying dramatic tumor shrinkage during primary therapy with octreotide LAR. Design and Setting: We characterized somatostatin and dopamine D2 receptor expression by immunohistochemistry and real-time RTPCR. The effects of different receptor-selective, bispecific analogs, and chimeric somatostatin/dopamine compounds on GH secretion and cell proliferation in primary cell cultures of the tumor were assessed. Results: The expression of SS receptor subtypes (sst)5 and D2 receptor was higher, compared with the other receptor subtypes. GH inhibition by SS-14 and the two chimeric somatostatin/dopamine compounds was scant but greater than subtype-selective and sst2/sst5 bispecific agonists. Conversely, cell growth was potently inhibited by all test substances. However, SS-14, sst2/sst5 bispecific agonist, and chimeric molecules were more potent than the other compounds. Conclusions: The significant antiproliferative effect of octreotide seems to be related to the higher expression of sst5 and the negligible antihormonal effect to the lower expression of sst2. However, activation of multiple receptors by new analogs may produce better control of tumor cell activities. The dissociation between antisecretive and antiproliferative effects observed in vivo and in vitro confirms that SSAs may induce tumor shrinkage despite the lack of effect on GH secretion.

Original languageEnglish
Pages (from-to)1592-1599
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number5
DOIs
Publication statusPublished - May 2007

Fingerprint

Octreotide
Pituitary Neoplasms
Technical presentations
Somatostatin
Tumors
Neoplasms
Dopamine
Somatostatin Receptors
Acromegaly
Primary Cell Culture
Dopamine D2 Receptors
Cell proliferation
Cell growth
Growth
Cell culture
Chemical activation
Immunohistochemistry
Cells
Cell Proliferation
Molecules

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Clinical case seminar : Rapid pituitary tumor shrinkage with dissociation between antiproliferative and antisecretory effects of a long-acting octreotide in an acromegalic patient. / Resmini, Eugenia; Dadati, Patrizia; Ravetti, Jean Luis; Zona, Gianluigi; Spaziante, Renato; Saveanu, Alexandru; Jaquet, Philippe; Culler, Michael D.; Bianchi, Federico; Rebora, Alberto; Minuto, Francesco; Ferone, Diego.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 92, No. 5, 05.2007, p. 1592-1599.

Research output: Contribution to journalArticle

Resmini, Eugenia ; Dadati, Patrizia ; Ravetti, Jean Luis ; Zona, Gianluigi ; Spaziante, Renato ; Saveanu, Alexandru ; Jaquet, Philippe ; Culler, Michael D. ; Bianchi, Federico ; Rebora, Alberto ; Minuto, Francesco ; Ferone, Diego. / Clinical case seminar : Rapid pituitary tumor shrinkage with dissociation between antiproliferative and antisecretory effects of a long-acting octreotide in an acromegalic patient. In: Journal of Clinical Endocrinology and Metabolism. 2007 ; Vol. 92, No. 5. pp. 1592-1599.
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AU - Dadati, Patrizia

AU - Ravetti, Jean Luis

AU - Zona, Gianluigi

AU - Spaziante, Renato

AU - Saveanu, Alexandru

AU - Jaquet, Philippe

AU - Culler, Michael D.

AU - Bianchi, Federico

AU - Rebora, Alberto

AU - Minuto, Francesco

AU - Ferone, Diego

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